Toxicity from illegitimate slimming agents - a 10-year case series at a tertiary toxicology laboratory in Hong Kong.

CONTEXT: This retrospective case-series study aims to provide an overview of the clinical, biochemical and analytical findings in patients who presented with toxicity related to the use of illegitimate slimming agents in Hong Kong from the perspective of a tertiary referral toxicology laboratory. METHODS: All clinical cases referred to the Hospital Authority Toxicology Reference Laboratory, Hong Kong with clinical suspicion of illegitimate slimming agent-related toxicity between January 2008 and December 2017 were reviewed retrospectively. The use of illegitimate slimming agents included the use of (1) deregistered slimming agents, (2) drug analogues that were not registered drugs, (3) registered drugs not approved for the indication of weight reduction (whether prescribed by a doctor or not), and (4) prescription-only slimming agents without a doctor's prescription. Patients taking registered weight-reducing drugs prescribed by a doctor were excluded. Patient demographics, clinical features, relevant laboratory investigations, and toxicological findings were analyzed. RESULTS: From 2008 to 2017, a total of 346 patients were analytically confirmed by our laboratory to have clinical toxicity related to the use of illegitimate slimming agents. The median age of the patients was 27 years and 92.5% of the patients were female. The most common clinical presentations included psychiatric features, sympathomimetic toxicity, hypokalemia, and abnormal thyroid function tests. Fatal or severe clinical toxicity was observed in 10% of the cases. The major classes of drugs detected on our analytical platforms were stimulants (e.g., sibutramine), laxatives (e.g., anthraquinones), diuretics (e.g., hydrochlorothiazide), and thyroid hormones (e.g., animal thyroid tissue). These illegitimate slimming agents were obtained from various sources including the Internet, over-the-counter in community pharmacy, or unspecified local sources. DISCUSSION AND CONCLUSIONS: The use of slimming agents is common worldwide; apart from taking registered slimming agents prescribed by registered practitioners, many users obtain slimming agents from various illegitimate sources. The unregulated use of these drugs can be associated with significant clinical toxicity. This study provides a current landscape of illegitimate slimming agent toxicity in Hong Kong to frontline clinicians and other toxicology professionals. Collaboration between clinicians, laboratories, and government authorities would be imperative to prevent further health adversities related to the misuse of these agents.

Caracterización de la consulta por intoxicación medicamentosa en los adolescentes en el Hospital Municipal de Bahía Blanca, Buenos Aires / Characterization of drug poisoning among adolescents seen at the municipal hospital of Bahía Blanca, Province of Buenos Aires, Argentina

Introducción. La consulta por intoxicación medicamentosa en los niños se da con frecuencia en los servicios de emergencias médicas; en la adolescencia, es cuando ocurren de forma intencional. Objetivo. Caracterizar los patrones epidemiológicos de la intoxicación medicamentosa en adolescentes ingresados al Hospital Municipal de Bahía Blanca. Material y método. Estudio descriptivo, basado en la revisión de historias clínicas de pacientes de 10 a 19 años que consultaron por intoxicación medicamentosa, entre los años 2012 y 2016. Las variables analizadas fueron edad, sexo, fármaco consumido, causa, manifestaciones clínicas y días de internación. Resultados. Se recopilaron 72 pacientes. La edad media fue de 16 años, razón mujer-hombre de 2,5:1. Predominaron las intoxicaciones por ansiolíticos (30%), seguidas de las polimedicamentosas (25%). El 95% manifestaron intención suicida, de los cuales el 55% ya tenían antecedentes. Conclusión. La intoxicación medicamentosa ocurrió, predominantemente, en mujeres, y se destacó el gran porcentaje de adolescentes que presentaba episodios previos.

Introduction. Drug poisoning among children is a frequent reason for visits to the emergency department; among adolescents, it is intentional. Objective. To describe the characteristics of drug poisoning among adolescents admitted to the municipal hospital of Bahía Blanca. Material and method. Descriptive study based on the review of medical records of patients aged 10-19 years seen for drug poisoning between 2012 and 2016. The following outcome measures were analyzed: age, sex, drug used, cause, clinical manifestations, and length of stay in days. Results. Data from 72 patients were collected. Their mean age was 16 years, and the female:male ratio was 2.5:1. Anxiolytic poisoning (30%) predominated, followed by polydrug use (25%). Ninety-five percent of patients showed a suicidal intention; of these, 55% had a history of suicide attempt. Conclusion. Drug poisoning was observed predominantly among girls; it is worth noting the high percentage of youth who had a history of suicide attempt.

Use of non-prescription analgesics and male reproductive function.

We studied the association between intake of non-prescription analgesics and semen quality and male reproductive hormone levels in a cross-sectional study among 1493 men. The men provided one semen (n=1493) and blood sample (n=1056) and filled in questionnaires on use of non-prescription analgesics (paracetamol, NSAIDs and combination drugs (yes/no)). Adjusting for age, study and other covariates, we observed no association between intake of non-prescription analgesics and markers of semen quality. Adjusting for age and time of day of blood sampling, users of non-prescription analgesics had a 10.4% (95% confidence interval (CI) 4.0-17.1%) higher testosterone level than non-users. When we stratified by medication type, the association between analgesics and higher testosterone was observed between users of non-steroidal anti-inflammatory drugs (NSAIDs) and combination drugs but not paracetamol. This study suggests that use of non-prescription analgesics is associated with slightly higher serum testosterone levels than non-use.

Potential toxicity of caffeine when used as a dietary supplement for weight loss.

BACKGROUND: Caffeine is added to dietary supplements to increase energy and suppress appetite. Many people take dietary supplements for weight loss. Patients may be unaware that supplements can contain caffeine, even if caffeine is not listed as an ingredient. Commonly used herbal dietary supplement ingredients, such as guarana, are natural sources of caffeine. OBJECTIVE: To describe a case of possible caffeine-induced seizure in a patient taking an over-the-counter weight loss supplement. CASE REPORT: A previously healthy 38-year-old female experienced blurring of vision and a new onset grand mal seizure. The patient had a two-month history of taking the dietary supplement, Zantrex - 3™. Zantrex - 3™ is advertised as a weight loss supplement which may provide rapid weight loss and extreme energy in one "power packed pill." CONCLUSIONS/SUMMARY: After discontinuation of Zantrex - 3™, the patient experienced no further seizure activity. Outpatient follow up at 2 and 6 weeks was noncontributory with follow up MRI and EEG both within normal limits.

Influence of sewage and pharmaceuticals on soil microbial function.

Although sewage effluent application to land is a common approach to recycle water and provide nutrients to plants, bioactive pharmaceuticals contained in sewage may change soil quality by affecting soil microbial communities. Establishing causal effects, however, is difficult, because trace levels of pharmaceuticals are confounded with other effluent constituents. Therefore, two originally similar soil microbial communities, one irrigated in situ with sewage effluent for 12 years and another nonirrigated, were exposed to high levels of acetaminophen, aspirin, carbamazepine, chlorpromazine, and tetracycline. The objectives of the current study were to determine the influence of high levels of pharmaceuticals on several soil microbial properties, the effect that prolonged effluent irrigation with ambient levels of pharmaceuticals had on soil microbial function, and how this effect would change in response to pharmaceutical exposure. Several pharmaceuticals, at high exposure levels, imposed stress on the soil microbial community as judged by increased CO(2) respiration, decreased biomass carbon, and altered substrate utilization affinities. Prolonged effluent irrigation, which altered the genetic fingerprint of the microbial community, also mitigated the response that exposure to pharmaceuticals had on the microbial community and enabled degradation of the antimicrobial salicylic acid after aspirin exposure. In conclusion, prolonged irrigation with sewage effluent containing pharmaceuticals at ambient levels influenced the microbial community so that they were able to better cope with sudden exposure to high levels of pharmaceuticals.

Diphenhydramine abuse and detoxification: a brief review and case report.

Many medicines available over the counter from pharmacies are known to have abuse potential, including diphenhydramine (DPH), an antihistamine with antimuscarinic properties used for the treatment of insomnia. We present a brief review of the literature describing DPH abuse, and report the case of GF, a 56 year old woman who was admitted to an inpatient addictions unit for detoxification from DPH. A literature search revealed five case reports of DPH abuse including a total of six patients, published between 1986 and 2001. All reported cases exhibited features of DSM-IV criteria for substance dependence, and there was an apparent link with antipsychotic usage. GF was treated with antipsychotics, and was using up to thirty 50 mg DPH tablets each day. She described feeling 'good and calm' and 'it stopped the tremors'. GF tolerated a gradual dose reduction schedule, and completed the detoxification programme relatively comfortably. She was discharged from the inpatient detoxification unit as planned, and had not relapsed at six months. The described case report highlights the importance of enquiring about non prescribed medication when taking a drug history. Similarly community pharmacists and GPs should be vigilant to excessive requests for DPH, particularly in patients with a psychotic illness.

Intoxication with over-the-counter antitussive medication containing dihydrocodeine and chlorpheniramine causes generalized convulsion and mixed acidosis.

We report a 35-year-old man who was referred to our hospital with generalized convulsion and mixed acidosis presumably caused by abuse of SS-BRON tablets, an over-the-counter (OTC) antitussive medication sold in Japan. These tablets contain dihydrocodeine phosphate, methylephedrine, chlorpheniramine, and caffeine. Although it is difficult to discern which component caused these symptoms, it seems that dihydrocodeine phosphate or methylephedrine was involved in the addiction to SS-BRON and chlorpheniramine may have caused the generalized convulsion. It should be recognized that an OTC antitussive, which is quite easy to obtain, can be abused and subsequently induce serious intoxication.

Legal piperazine-containing party pills--a new trend in substance misuse.

In this Harm Reduction Digest Sheridan, Butler, Wilkins and Russell address the emergent phenomenon of so-called 'legal party pills' which have become a significant drug issue in New Zealand and elsewhere. Although banned in a number of countries, they are currently legally available in New Zealand where they are marketed as 'safe' alternatives' to 'illicit' drugs often used in the dance scene such as MDMA and amphetamines. The authors describe the availability and use of these substances in New Zealand, summarize what is known about their effects, and speculate on harm reduction interventions and mechanisms of control and their possible sequelae. The paper provides a timely account of an emerging drug issue of relevance to harm reduction internationally.

Final report on the safety assessment of Hexamidine and Hexamidine Diisethionate.

Hexamidine Diisethionate functions as a biocide in cosmetics at concentrations of 0.03% to 0.1% in 38 cosmetic products. Hexamidine functions as a biocide and preservative in cosmetics, but is not in current use in cosmetics, but it is used in over-the-counter (OTC) drug products. Hexamidine was poorly absorbed by human cadaver skin when in water-oil formulations or in a gel that simulated a cosmetic product formulation. Hexamidine Diisethionate was poorly absorbed by the skin of live rats and was not stored in any tissue type. Hexamidine Diisethionate given to rats intravenously was rapidly metabolized to Hexamidine. Excretion was primarily via the feces, with a small amount excreted in the urine. Acute oral LD(50) values of Hexamidine Diisethionate were 0.71 to 2.5 g/kg in mice and 0.75 g/kg in rats. Dermal exposure to 4 g/kg Hexamidine Diisethionate in rats or up to 9.4 ml/kg of a 0.1% Hexamidine Diisethionate solution under occlusion in rabbits produced no mortality or other signs of toxicity. The no-observed-effect level (NOEL) for oral subchronic toxicity of Hexamidine Diisethionate in rats was 50 mg/kg/day. No signs of toxicity were observed with 2% Hexamidine Diisethionate in subchronic studies using rabbits. Application of 0.1 ml of 0.11% Hexamidine Diisethionate in aqueous solution to the eyes of rabbits produced transient reactions; 0.05% produced no reactions. Slight erythema was observed with 0.10% Hexamidine Diisethionate applied to the abraded skin of 1/11 albino rabbits. A 40% solution of Hexamidine Diisethionate applied to 10% of the body surface of rats produced slight erythema, slight edema, and scabbing in some animals at varying times after treatment. Hexamidine Diisethionate was not a sensitizer in the guinea pig maximization test or in an intracutaneous guinea pig sensitization test. Hexamidine Diisethionate was not a photosensitizer in albino rabbits. Hexamidine Diisethionate was not mutagenic in a bacterial reverse mutagenicity assay or clastogenic in mammalian cells. Hexamidine Diisethionate at 0.10% did not provoke primary irritation, inflammation, or sensitization in a clinical test of 200 human subjects. One case report of photosensitivity to Hexamidine and one of contact sensitivity to Hexamidine were reported. There were nine case reports of contact sensitivity to Hexamidine Diisethionate. A European safety assessment recommended a limit of 0.1% Hexamidine Diisethionate in leave-on and rinse-off cosmetic products. In considering the available data, the Cosmetic Ingredient Review (CIR) Expert Panel acknowledged the lack of carcinogenicity and reproductive/developmental toxicity data. Because genotoxicity studies were negative, and there were no structural alerts, the Panel concluded that it was unlikely that these ingredients would be carcinogenic. Because the rate of absorption of Hexamidine and Hexamidine Diisethionate is slow, there is no tissue accumulation, and excretion is rapid and complete, and there was no toxicity in a subchronic study, the Panel concluded that dermal exposures would not likely present a risk of reproductive/developmental toxicity. The Panel noted that a guinea pig maximization study using Hexamidine Diisethionate produced no dermal reactions and that a clinical test at 0.1% produced no irritation or sensitization. The Panel also expressed concern regarding the possible presence of 1,4-dioxane as an impurity, and stressed that the cosmetic industry should continue to use the necessary purification procedures to remove these impurities from the ingredient before blending into cosmetic formulations. The Panel noted that there are no data for concentration of use for eye makeup and baby products, and was concerned that there should not be unrestricted concentration levels in these product categories. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used and at what concentration indicate a pattern of use. Within this overall pattern of use, the Expert Panel considers all ingredients in this group to be safe at concentrations up to and including 0.1%.

Topical steroid abuse: its use as a depigmenting agent.

This study was undertaken to document prevalence, motives and observed complications of steroid use as a depigmenting agent amongst African blacks in southeast Nigeria. This practice is very common in the African environment. Consecutive new patients attending the dermatology clinic of the University of Nigeria TeachingHospital, Enugu, from June to December 2004 were recruited. Active substances of products used were determined from packages, while unknown concoctions were analyzed. Chi-squared and Fischer tests were used for statistical analysis, with a significant threshold fixed at 5%. Females aged 18-69 years accounted for 75% (414) of patients. Main topical steroids used by both women and men were class-1 steroids, and these were often compounded with other bleaching products. Median duration of usage was 9 years +/- 1.3. Disorders observed included steroid-induced acne (45.3%), macular hyperpigmentation of face (37.2%), mycoses (40.4%), striae (28.3%), telangiectasis (21.3%), hypertrichosis (13.9%) and diabetes mellitus (2.1%). Duration of utilization of these topical steroids was significantly associated with severe local and systemic consequences, while withdrawal of the offending steroids usually resulted in severe withdrawal dermatitis that was unpleasant to patients. This may suggest that discontinuation is impossible.

Dextromethorphan psychosis, dependence and physical withdrawal.

As part of a synthesis of evidence regarding the abuse and addiction liability of dextromethorphan (DM), an over-the-counter cough medicine available in over 140 preparations, an uncommonly published case of dextromethorphan dependence (addiction) is described, with specific, rarely published complications. The individual was interviewed and several medical databases were also reviewed (Medline, 1966-present; PubMed) for all content relating to the Keywords: dextromethorphan, abuse, dependence, cough medicine, addiction, withdrawal, psychosis. The patient evidenced history suggesting substance dependence, substance-induced psychosis and substance withdrawal in relation to DM. A literature review revealed that DM has specific serotonergic and sigma-1 opioidergic properties. Dextrorphan (DOR), the active metabolite of DM, has similar properties; however, DOR is a weaker sigma opioid receptor agonist, and a stronger NMDA receptor antagonist. DM and DOR display specific biological features of addiction, and are capable of inducing specific psychiatric sequelae. A specific, reproducible toxidrome with significant psychiatric effects occurred, when DM was abused at greater than indicated doses, with more profound and potentially life-threatening effects at even higher doses. DM withdrawal appears evident. DM's active metabolite, DOR, has pharmacodynamic properties and intoxication effects similar to dissociatives, and may be more responsible for the dissociative effect that this DM abuser sought. However, it is this same metabolite that may be fraught with the potentially life-threatening psychoses and dissociative-induced accidents, as well as addiction. While DM has been hypothesized as the most commonly abused dissociative, health-care providers seem largely unaware of its toxidrome and addiction liability.

Over-the-counter cold medications-postmortem findings in infants and the relationship to cause of death.

The Montgomery County Coroner's Office has encountered a series of 10 infant deaths over an 8-month period in infants under 12 months old with toxicology findings that include a variety of drugs commonly found in over-the-counter (OTC) cold medications. The drugs detected were ephedrine, pseudoephedrine, dextromethorphan, diphenhydramine, chlorpheniramine, brompheniramine, ethanol, carbinoxamine, levorphanol, acetaminophen, and the anti-emetic metoclopramide. Toxicology findings were confirmed in 2 different matrices in 9 of the 10 cases and by 2 different analytical methods. The blood concentrations of the drugs and the case histories, as well as the cause of death for each infant, if available, will be given. The majority of these deaths were either toxicity from the OTC cold medications directly or as a contributory factor in the cause of death. Only two of the cases were the result of possible child abuse. Caregivers may be under the mistaken notion that OTC cold medications formulated for children are also safe for use in infants. These cases demonstrate that not only is administration of some OTC cold medications not safe, but use of OTC cold medications in infants can result in toxicity that can lead to death.

Safety of 5-hydroxy-L-tryptophan.

5-Hydroxy-L-tryptophan (5-HTP) is the immediate precursor in the biosynthesis of 5-hydroxy-tryptamine (5-HT; serotonin) from the essential amino acid L-tryptophan (L-Trp). The use of L-Trp as a dietary supplement was discontinued in 1989 due to an outbreak of eosinophilia-myalgia syndrome (EMS) that was traced to a contaminated synthetic L-Trp from a single manufacturer. 5-HTP has since become a popular dietary supplement in lieu of the removal of L-Trp from the market. Because of its chemical and biochemical relationship to L-Trp, 5-HTP has been under vigilance by consumers, industry, academia and government for its safety. However, no definitive cases of toxicity have emerged despite the worldwide usage of 5-HTP for last 20 years, with the possible exception of one unresolved case of a Canadian woman. Extensive analyses of several sources of 5-HTP have shown no toxic contaminants similar to those associated with L-Trp, nor the presence of any other significant impurities. A minor chromatographic peak (peak X) reported in some 5-HTP samples lacks credibility due to chromatographic artifacts and infinitesimal concentrations, and has raised undue speculations concerning its chemistry and toxicity.